A role of nicotinic acetylcholine receptors (nAChR) in the development of Parkinson's disease (PD) has been investigated using two mouse models corresponding to the presymptomatic stage and the early symptomatic stage of PD. Quantitative determination of nAChR in the striatum and substantia nigra (SN) was performed using the radioactive derivatives of epibatidine, -conotoxin MII, and -bungarotoxin as ligands. The number of ligand-binding sites changed differently depending on their location in the brain, the stage of the disease and the receptor subtype. Epibatidine binding decreased in the striatum to 66% and 70% at the presymptomatic and early symptomatic stages, respectively, whereas in SN a 160% increase was registered at the presymptomatic stage. The -conotoxin MII binding on striatal dopaminergic axonal terminals at the presymptomatic stage decreased by 20% and at the symptomatic stage it demonstrated a further decrease. The increase in -bungarotoxin binding at the presymptomatic stage and a decrease at the early symptomatic stage was observed in the striatum. In SN, the level of -bungarotoxin binding decreased at the presymptomatic stage and kept constant at the symptomatic stage. The significant decrease in the expression of Chrna4 and Chrna6 genes encoding 4 and 6 nAChR subunits was observed in SN at the early symptomatic stage, while a 13-fold increase in expression of the Chrna7 gene encoding the 7 nAChR subunit was detected at the presymptomatic stage. The data obtained suggest possible involvement of nAChR in compensatory mechanisms at early PD stages.
Issledovana rol' nikotinovykh atsetilkholinovykh retseptorov (nAKhR) na rannikh stadiiakh bolezni Parkinsona (BP) na éksperimental'nykh modeliakh u mysheĭ, sootvetstvuiushchikh dosimptomnoĭ i ranneĭ simptomnoĭ stadiiam BP. Kolichestvennoe opredelenie nAKhR v preparatakh striatuma i chernoĭ substantsii (ChS) provodili s pomoshch'iu ligandov, selektivnykh dlia razlichnykh podtipov nAKhR: radioaktivnykh proizvodnykh épibatidina, -konotoksina MII i -bungarotoksina. Kolichestvo vyiavlennykh ligand-sviazyvaiushchikh saĭtov zaviselo ot ikh tipa, lokalizatsii v golovnom mozge i stadii zabolevaniia. V striatume sviazyvanie épibatidina na dosimptomnoĭ i ranneĭ simptomnoĭ stadiiakh snizheno na 66% i 70% sootvetstvenno, a v ChS – povysheno do 160% na dosimptomnoĭ stadii po sravneniiu s kontrolem. Sviazyvanie -konotoksina MII na terminaliakh aksonov dofaminergicheskikh neĭronov na dosimptomnoĭ stadii bylo snizheno na 20%, i snizhenie ikh kolichestva prodolzhilos' na ranneĭ simptomnoĭ stadii. Sviazyvanie -bungarotoksina v striatume povysheno na dosimptomnoĭ i snizheno na ranneĭ simptomnoĭ stadiiakh, a v ChS umen'shalos' uzhe na dosimptomnoĭ stadii i ostavalos' postoiannym. Znachitel'noe snizhenie ékspressii genov neĭronal'nykh nAKhR Chrna4 i Chrna6, kodiruiushchikh 4 i 6 sub"edinitsy nAKhR, otmecheno v ChS na ranneĭ simptomnoĭ stadii, a dlia gena Chrna7, kodiruiushchego 7 sub"edinitsu, obnaruzheno 13-kratnoe uvelichenie na dosimptomnoĭ stadii. Poluchennye dannye ob izmeneniiakh urovnia mRNK ili funktsional'nykh kholinoretseptorov svidetel'stvuiut o vozmozhnom uchastii nAKhR v kompensatornykh mekhanizmakh na rannikh stadiiakh BP.
Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; dopaminergic neuron; nicotinic acetylcholine receptors; striatum; substantia nigra.